2-Bromo-2-methylpropanoic acid → Pyrazole
Reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([C:7]([CH3:14])([CH3:13])[C:8]([O:10]CC)=[O:9])[CH:6]=1.BrC(C)(C)C(O)=O>>[NH:4]1[CH:3]=[CH:2][CH:6]=[N:5]1.[CH3:14][C:7]([N:5]1[CH:6]=[CH:2][CH:3]=[N:4]1)([CH3:13])[C:8]([OH:10])=[O:9]Participants
Procedure
Scheme 7 shows the synthesis of ethyl 2-(4-bromo-1H-pyrazol-1-yl)-2-methylpropanoate IV starting from 2-bromo-2-methylpropanoic acid 15. Alkylation of pyrazole with 15 gave 2-methyl-2-(1H-pyrazol-1-yl)propanoic acid 16 (Example 12). Esterification of 16 with sulfuric acid in ethanol gave ethyl 2-methyl-2-(1H-pyrazol-1-yl)propanoate 17 (Example 13). Regiospecific bromination of 17 with N-bromosuccinimide (NBS) gave IV (Example 14). Alternatively, 16 was treated in situ with a brominating reagent such as 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) to give 2-(4-bromo-1H-pyrazol-1-yl)-2-methylpropanoic acid which was esterified to give IV, where R is ethyl. Other esters can also be prepared, such as methyl, iso-propyl, or any alkyl, benzyl or aryl ester.
Sources & evidence
- ORD record
- ord-083072b6565e4924a7d2eaf7d2dcb457
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09303043B2
Reaction notes
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